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Bridging Space and Time: Resolving the Temporal Dynamics of the Seminiferous Epithelial Cycle Using Spatial Transcriptomics
Bridging Space and Time: Resolving the Temporal Dynamics of the Seminiferous Epithelial Cy...
Bridging Space and Time: Resolving the Temporal Dynamics of the Seminiferous Epithelial Cycle Using Spatial Transcriptomics

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202104749
ISBN  
9798290652931
DDC  
591
저자명  
Chakravorty, Arun.
서명/저자  
Bridging Space and Time: Resolving the Temporal Dynamics of the Seminiferous Epithelial Cycle Using Spatial Transcriptomics
발행사항  
[Sl] : California Institute of Technology, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
131 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-01, Section: B.
주기사항  
Advisor: Cai, Long.
학위논문주기  
Thesis (Ph.D.)--California Institute of Technology, 2025.
초록/해제  
요약Biology is inherently spatial, with tissue architecture and cell-cell interactions shaping dynamic developmental and homeostatic processes. In this thesis, we harness high-resolution spatial transcriptomics via RNA seqFISH+ to show how spatial information can be used to resolve temporal information in complex tissues, using adult mouse spermatogenesis as a model. By profiling 2,638 genes in over 216,000 cells, we find that each seminiferous tubule cross-section represents a distinct timepoint of the seminiferous epithelial cycle, and collectively all tubules form a circular topology in gene expression space that precisely aligns with the known 12-stage progression. Intriguingly, Sertoli cells exhibit a robust cyclic transcriptional program synchronized with germ cell differentiation, raising the question of whether this cycle is driven solely by germ cells or whether Sertoli cells display an intrinsic cyclic expression profile. To address this, we ablate differentiating germ cells using a DNA alkylating agent, busulfan. In this model, despite the lack of differentiating germ cells, Sertoli cells maintain much of their cyclic expression suggesting an autonomous cycle that partially dephases without germ cell input. Integrative analyses suggest that the underlying mechanism of this oscillation may involve an innate retinoic acid metabolic cycle and/or an interconnected transcription factor network. Finally, we discuss how these findings broaden our understanding of tissue processes and propose that spatial transcriptomics can be adopted to reconstruct temporal dynamics for many tissues from static snapshots.
일반주제명  
Embryos
일반주제명  
Gene expression
일반주제명  
Bar codes
일반주제명  
Spermatogenesis
일반주제명  
Hybridization
일반주제명  
Insects
일반주제명  
Biology
일반주제명  
Genomics
일반주제명  
Stem cells
일반주제명  
Geometry
일반주제명  
Morphology
일반주제명  
Cell division
기타저자  
California Institute of Technology Biology and Biological Engineering
기본자료저록  
Dissertations Abstracts International. 87-01B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aChakravorty,  Arun.
■24510▼aBridging  Space  and  Time:  Resolving  the  Temporal  Dynamics  of  the  Seminiferous  Epithelial  Cycle  Using  Spatial  Transcriptomics
■260    ▼a[Sl]▼bCalifornia  Institute  of  Technology▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a131  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-01,  Section:  B.
■500    ▼aAdvisor:  Cai,  Long.
■5021  ▼aThesis  (Ph.D.)--California  Institute  of  Technology,  2025.
■520    ▼aBiology  is  inherently  spatial,  with  tissue  architecture  and  cell-cell  interactions  shaping  dynamic  developmental  and  homeostatic  processes.  In  this  thesis,  we  harness  high-resolution  spatial  transcriptomics  via  RNA  seqFISH+  to  show  how  spatial  information  can  be  used  to  resolve  temporal  information  in  complex  tissues,  using  adult  mouse  spermatogenesis  as  a  model.  By  profiling  2,638  genes  in  over  216,000  cells,  we  find  that  each  seminiferous  tubule  cross-section  represents  a  distinct  timepoint  of  the  seminiferous  epithelial  cycle,  and  collectively  all  tubules  form  a  circular  topology  in  gene  expression  space  that  precisely  aligns  with  the  known  12-stage  progression.  Intriguingly,  Sertoli  cells  exhibit  a  robust  cyclic  transcriptional  program  synchronized  with  germ  cell  differentiation,  raising  the  question  of  whether  this  cycle  is  driven  solely  by  germ  cells  or  whether  Sertoli  cells  display  an  intrinsic  cyclic  expression  profile.  To  address  this,  we  ablate  differentiating  germ  cells  using  a  DNA  alkylating  agent,  busulfan.  In  this  model,  despite  the  lack  of  differentiating  germ  cells,  Sertoli  cells  maintain  much  of  their  cyclic  expression  suggesting  an  autonomous  cycle  that  partially  dephases  without  germ  cell  input.  Integrative  analyses  suggest  that  the  underlying  mechanism  of  this  oscillation  may  involve  an  innate  retinoic  acid  metabolic  cycle  and/or  an  interconnected  transcription  factor  network.  Finally,  we  discuss  how  these  findings  broaden  our  understanding  of  tissue  processes  and  propose  that  spatial  transcriptomics  can  be  adopted  to  reconstruct  temporal  dynamics  for  many  tissues  from  static  snapshots.
■590    ▼aSchool  code:  0037.
■650  4▼aEmbryos
■650  4▼aGene  expression
■650  4▼aBar  codes
■650  4▼aSpermatogenesis
■650  4▼aHybridization
■650  4▼aInsects
■650  4▼aBiology
■650  4▼aGenomics
■650  4▼aStem  cells
■650  4▼aGeometry
■650  4▼aMorphology
■650  4▼aCell  division
■690    ▼a0287
■690    ▼a0306
■690    ▼a0729
■71020▼aCalifornia  Institute  of  Technology▼bBiology  and  Biological  Engineering.
■7730  ▼tDissertations  Abstracts  International▼g87-01B.
■790    ▼a0037
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358768▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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